title: The structure of a membrane fusion mutant of the influenza virus haemagglutinin.
abstract: The haemagglutinin glycoprotein (HA) of influenza virus specifically mediates fusion of the viral and host cell endosomal membranes at the acidic pH of endosomes. The HAs from mutant viruses with raised fusion pH optima contain amino acid substitutions in regions of the HA structure thought to be involved in the fusion process [Daniels et al. (1985b) Cell, 40, 431-439]. We have determined the neutral pH crystal structure of one such mutant, HA2 112 Asp----Gly. A water molecule appears to partially replace the aspartate side chain, and no changes are observed in the surrounding structure. It appears that four intra-chain hydrogen bonds that stabilize the location of the N-terminus of HA2 are lost in the mutant, resulting in a local destabilization that facilitates the extrusion of the N-terminus at higher pH.
authors.affiliation: Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, MA 02138.
authors.forename: W I
authors.initials: WI
authors.lastname: Weis
authors.forename: S C
authors.initials: SC
authors.lastname: Cusack
authors.forename: J H
authors.initials: JH
authors.lastname: Brown
authors.forename: R S
authors.initials: RS
authors.lastname: Daniels
authors.forename: J J
authors.initials: JJ
authors.lastname: Skehel
authors.forename: D C
authors.initials: DC
authors.lastname: Wiley
mesh_terms: D003460:Crystallization; D003461:Crystallography; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000235:genetics; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D015394:Molecular Structure; D009154:Mutation; D011487:Protein Conformation; D014759:Viral Envelope Proteins
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D014759:Viral Envelope Proteins